Abstract
Camptothecin (CPT) derivatives have become integral to the management of lung and colon cancer. They continue to be the subject of intense investigation. The parent compound, CPT, was extracted from the leaves of Camptotheca acuminata by Wall and Wani in 1957. The hydrophilic carboxylate salt entered clinical trials in the late 1960s. The lack of efficacy and unpredictable bone marrow and bladder toxicity halted its clinical development (1). When topoisomerase I (TOP-I) was discovered as the target of CPT class of compounds 1985 (2), there was a resurgence of interest in the compound.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Muggia FM, Creaven PJ, Hansen HH, Cohen MH, Selawry OS. 1972 Phase I trial of weekly and daily treatment with camptothecin (NSC-100880): correlation with preclinical studies. Cancer Chemother Rep 56:515–521.
Hsiang YH, Hertzberg R, Hecht S, Liu LF. 1985 Camptothecin induces proteinlinked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 260:14873–14878.
Liu LF. 1989 DNA topoisomerase poisons as anti-tumor drugs. Ann Rev Biochem 58:351–375.
Zhang H, D’Arpa P, Liu LF. 1990 A model for tumor cell killing by topoisomerase poisons. Cancer Cells 2:23–27.
Borovitskaya AE, D’Arpa P. 1998 Replication-dependent and-independent camptothecin cytotoxicity of seven human colon tumor cell lines. Oncol Res 10:271–276.
Holm C, Covey JM, Kerrigan D, Pommier Y. 1989 Differential requirement of DNA replication for the cytotoxicity of DNA topoisomerase I and II inhibitors in Chinese hamster DC3F cells. Cancer Res 49: 6365–3638.
Desai SD, Liu LF, Vazquez-Abad D, D’Arpa P. 1997 Ubiquitin-dependent destruction of topoisomerase I is stimulated by the antitumor drug camptothecin. J Biol Chem 272:24159–24164.
Murren JR, Beidler DR, Cheng YC. 1996 Camptothecin resistance related to druginduced down-regulation of topoisomerase I and to steps occurring after the formation of protein-linked DNA breaks. Ann NY Acad Sci 803: 74–92.
Liu LF, Desai SD, Li TK, Mao Y, Sun M, Sim SP. 2000 Mechanism of action of camptothecin. Ann N Y Acad Sci 922:1–10.
Wall ME. 1998 Camptothecin and taxol: discovery to clinic. Med Res Rev 18:299–314.
Mi Z, Burke TG. 1994 Differential interactions of camptothecin lactone and carboxylate forms with human blood components. Biochemistry 33:10325–10336.
Mi Z, Burke TG. 1994 Marked interspecies variations concerning interactions of camptothecin with serum albumin. Biochemistry 33:12540–12545.
Jaxel C, Kohn KW, Wani MC, Wall ME, Pommier Y. 1989 Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res 49:1465–1469.
Hertzberg RP, Caranfa MJ, Holden KG, et al. 1989 Modifications of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem 32:715–720.
Lavergne O, Lesueur-Ginot L, Rodas F, et al. 1998 Homocamptothecins, synthesis and antitumor activity of novel E-ring-modified camptothecin analogues. J Med Chem 41:5410–5419.
Wang X, Zhou X, Hecht SM. 1999 Role of the 20-hydroxyl group in camptothecin binding by the topoisomerase I-DNA binary complex. Biochemistry 38:4374–4381.
Tanizawa A, Fujimori A, Fujimori Y, Pommier Y. 1994 Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst 86:836–82.
Tanizawa A, Kohn KW, Kohlhagen G, Leteurtre F, Pommier Y. 1995 Differential stabilization of eukaryotic DNA topoisomerase I cleavable complexes by camptothecin derivatives. Biochemistry 34:7200–7206.
ten Bokkel Huinink W, Gore M, Carmichael J, et al. 1997 Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol 15:2183–2193.
Rothenberg ML, Cox JV, DeVore RF, et al. 1999 A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer 85:786–795.
Rougier P, Bugat R, Douillard JY, et al. 1997 Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy. J Clin Oncol 15:251–260.
Emerson DL, Besterman JM, Brown HR, et al. 1995 In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res 55:603–609.
Gerrits CJ, Creemers GJ, Schellens JH, et al. 1996 Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration. Br J Cancer 73:744–750.
Gerrits CJ, Schellens JH, Creemers GJ, et al. 1997 The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor. Br J Cancer 76:946–951.
Eckhardt SG, Baker SD, Eckardt JR, et al. 1998 Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin analogue, administered for five consecutive days every three weeks. Clin Cancer Res 4: 595–604.
Paz-Ares L, Kunka R, DeMaria D, et al. 1998 A phase I clinical and pharmacokinetic study of the new topoisomerase inhibitor GI147211 given as a 72-h continuous infusion. Br J Cancer 78:1329–1336.
Stevenson JP, DeMaria D, Sludden J, et al. 1999 Phase I/pharmacokinetic study of the topoisomerase I inhibitor GG211 administered as a 21-day continuous infusion. Ann Oncol 10:339–344.
Gamucci T, Paridaens R, Heinrich B, et al. 2000 Activity and toxicity of GI147211 in breast, colorectal and non-small-cell lung cancer patients: an EORTC-ECSG phase II clinical study. Ann Oncol 11:793–797.
Gupta E, Luo F, Lallo A, et al. 2000 The intestinal absorption of camptothecin, a highly lipophilic drug, across Caco-2 cells is mediated by active transporter(s). Anticancer Res 20:1013–1016.
Brangi M, Litman T, Ciotti M, et al. 1999 Camptothecin resistance: role of the ATPbinding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res 59:5938–5946.
Koike K, Kawabe T, Tanaka T, et al. 1997 A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells. Cancer Res 57:5475–5479.
Massing U, Fuxius S. 2000 Liposomal formulations of anticancer drugs: selectivity and effectiveness. Drug Resist Updat 3:171–177.
Burke TG, Staubus AE, Mishra AK. 1992 Liposomal stabilization of camptothecin’s lactone ring. J Am Chem Soc 114:8318–8319.
Burke TG. Liposomal and micellar stabilization of camptothecin drugs. U.S. Patent 5,552,156. September 3, 1996.
Colbern GT, Dykes DJ, Engbers C, et al. 1998 Encapsulation of the topoisomerase I inhibitor GL147211C in pegylated (STEALTH) liposomes: pharmacokinetics and antitumor activity in HT29 colon tumor xenografts. Clin Cancer Res 4:3077–3082.
Emerson DL, Bendele R, Brown E, et al. 2000 Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan. Clin Cancer Res 6:2903–2912.
Desjardins JP, Abbott EA, Emerson DL, et al. 2001 Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice. Anticancer Drugs 12:235–245.
Emerson DL, Bendele R, Brown E, et al. 2001 In vivo antitumor efficacy of liposomal lurtotecan (NX 211) in human xenografts. Proc Am Assoc Cancer Res 42:545.
Bos AM, Kehrer D, Sparreboom A, et al. 2000 Phase I study of NX 211 (liposomal lurtotecan) administered as a single dose every 3 weeks. Proc Am Soc Clin Oncol 19:768.
Rothenberg ML, Gelmon KA, Eisenhauer E, et al. 2000 Phase I evaluation of liposomal topoisomerase I inhibitor, NX 211, given on days 1,2,3 or days 1,8 every 3 weeks to patients with advanced solid tumors. Proc Am Soc Clin Oncol 19:769.
Eisenhauer EA, Verweij J, Rothenberg ML, et al. 2001 Phase I evaluation of liposomal topoisomerase I inhibitor, NX 211, administered by three schedules to patients with advanced solid tumors. Proc Am Soc Clin Oncol 19:409.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Flaherty, K.T., Stevenson, J.P., Twelves, C.J., O’Dwyer, P.J. (2005). The Clinical Development of Lurtotecan. In: Adams, V.R., Burke, T.G. (eds) Camptothecins in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-866-8:301
Download citation
DOI: https://doi.org/10.1385/1-59259-866-8:301
Publisher Name: Humana Press
Print ISBN: 978-1-58829-027-4
Online ISBN: 978-1-59259-866-3
eBook Packages: MedicineMedicine (R0)